Tyrosinase inhibitors from plants

ABSTRACT

The present invention provides tyrosinase inhibiting extracts from dictotyledonous plant species indigenous to Canada and compositions containing the extracts for the treatment of skin, particularly skin lightening. The present invention also provides a method of detecting tyrosinase activity in an extract of a dicotyledonous plant species indigenous to Canada.

RELATED APPLICATIONS

This application is the national phase of PCT/CA99/00530, filed Jun. 8,1999, designating the U.S. and published as WO 99/64025, claimingpriority from U.S. patent application Ser. No. 60/088,484, filed Jun. 8,1998. All of the foregoing applications, as well as all documents citedin the foregoing applications (“application documents”) and alldocuments cited or referenced in application documents are herebyincorporated herein by reference. Also, all documents cited in thisapplication (“herein cited documents”) and all documents cited orreferenced in herein cited documents are hereby incorporated herein byreference.

FIELD OF THE INVENTION

The invention relates to a product comprising a tyrosinase inhibitingextract derived from a dicotyledonous plant species indigenous toCanada. The present invention also relates to compositions comprisingthe product and a suitable diluent or carrier for the treatment of skinor of fruit, vegetables or beverages. The present invention furtherrelates to a method for identifying plant extracts that are capable ofinhibiting the enzyme tyrosinase.

BACKGROUND OF THE INVENTION

Tyrosinase (tyrosine oxidase, EC 1.10.3.1) is an enzyme or closelyhomologous group of enzymes of universal occurrence in microbes, plantsand animals. Its primary metabolic function is to catalyze the oxidativedegradation of the amino acid tyrosine. This degradation takes slightlydifferent routes in animals, plants and microbes, but therate-controlling first steps—those catalyzed by tyrosinase—are the samein virtually all living species. In animals, including man, tyrosinasefirst transforms tyrosine into 3,4-dihydroxyphenylalanine (DOPA), thenceto the corresponding quinone (DOPAquinone), and finally to2-carboxy-2,3-dihydroindole-5,6-quinone (DOPAchrome) which is furtherconverted by other enzymes to still more highly oxidized materials whichinclude the melanin substances responsible for skin pigmentation.

Skin pigmentation thus depends upon the action of tyrosinase. If thisenzyme is not active, normal pigmentation does not occur, and skin losesor fails to acquire its normal tan-to-brown coloration. The effect isindependent of racial or environmental factors. Pigmentation lossmanifests itself in lentigo senile, so-called “age spots”, asmall-scale, patchy color loss often seen in skin of people over 50years of age; typically the de-pigmented patches will be 1-3 mm acrossand can be very numerous. A more serious effect is leucodenna, a groupof diseases in which large areas of skin lose their melanin and appearpink. An extreme effect is albinism, a condition in which tyrosinaseenzyme is entirely dysfunctional and no pigmentation of skin (or eyes orhair) occurs.

If on the other hand tyrosinase activity is accelerated, as insun-tanning or in some pathological conditions, the amount of melaninformed increases and skin color darkens. When the distribution of thenew melanin is even and controlled, the result is a “glorious bronzedbody”; but if the new melanin is patchy or produced uncontrollably, theresult is pathological. Skin melanomas are sites of localizedhyperactivity by tyrosinase; they are often associated with cancerouscell modification. The causal relationship of tyrosinase action to skinpigmentation was established many years ago (Mason, H. S. (1948) J.Biol. Chem. 172, 83-86; Balin, A. K. and Kligman, A. M. (1989) Aging andthe Skin 372pp, Raven Press, N.Y.) and is now well-understood.

Materials which suppress the action of tyrosine oxidase are presumed toslow the build-up of skin spots over time, and this presumption isvindicated by scientific evidence. Thus, the correlation betweentyrosinase inhibition and protection of skin against unwantedpigmentation is accepted by the medical profession and by the cosmeticindustry.

In addition to its skin functions, tyrosinase is active in other typesof living tissue in the turnover metabolism of tyrosine and in theproduction of pigmented materials in those tissues.

With respect to cosmetics, skin lightening and skin darkening have beenpracticed since earliest times, and today these are mainstays of somesectors of the world cosmetics industry. Skin lightening hastraditionally been accomplished by rigorously excluding sunlight fromskin, or by the use of chemical lightening agents. One such agent issynthetic hydroquinone (1,4-dihydroxybenzene). This substance isconsidered the cosmetic industry standard for tyrosinase inhibitionpotency.

SUMMARY OF THE INVENTION

Prior to the present invention, the possibility of finding effectivetyrosinase inhibitors in dicotyledonous plant species indigenous toCanada had not been appreciated.

Accordingly, the present invention provides a product comprising anextract derived from a dicotyledonous plant species indigenous toCanada, wherein the extract inhibits tyrosinase. Preferably, the extractis derived from a plant species selected from Polygonaceae, Rosaceae andOnagraceae. The extract is preferably derived from one or more parts ofthe plant selected from leaves, twigs, flowers, flowering aerials,fruiting aerials, seeding aerials, roots and fruits.

Preferably, the extract is derived from the group consisting of:

flowering aerials of Artemisia campestris (plains wormwood);

flowering aerials of Aster ericoides (white prairie aster);

flowering aerials of Aster hesperius (willow aster);

leaves, twigs and flowers of Cornus stolonifera (red-osier dogwood);

leaves and twigs of Cotoneaster acutifolia (cotoneaster);

flowering aerials of Epilobium angustifolium (fireweed);

seeding aerials of Euphorbia esula (leafy spurge);

fruiting aerials of Fragaria americana (wild strawberry);

fruiting aerials of Fragaria glauca (Wild strawberry);

flowering aerials of Geranium bicknelli (Bicknell's geranium);

flowering aerials of Geum aleppicum (yellow avens);

flowering aerials of Geum triflorum (3-flowered avens);

flowering aerials of Glycyrrhiza lepidota (wild licorice);

flowering aerials of Hedysarum americanum (American hedysarum);

roots of Heuchera richardsonii (alumroot);

flowering aerials of Oenothera biennis (yellow evening-primrose);flowering aerials of Polygonum persicaria (lady's-thumb);

flowering aerials of Potentilla fruticosa (shrubby cinquefoil);

flowering aerials of Potentilla norvegica (rough cinquefoil);

flowering aerials of Rosa acicularis (prairie rose);

fruiting aerials of Rosa arkansana (low rose);

fruiting aerials of Rumex maritimus (golden dock);

fruiting aerials and flowering aerials of Rumex occidentalis (westernfield dock);

fruiting aerials and fruits of Rumex pseudonatronatus (field dock); and

fruits of Rumex stenophyllus (narrow-leaved dock).

The present invention also provides a composition comprising the productas defined herein, together with a cosmetically or pharmaceuticallyacceptable, or edible, diluent or carrier. The composition is preferablyfor cosmetic treatment of skin or for inhibiting browning of edibleproducts. The composition is more preferably for skin lightening, evenmore preferably to reduce melanin and/or melanogenesis. The at least oneplant extract in the composition is preferably selected from the groupconsisting of:

fruiting aerials of Rumex maritimus (golden dock);

fruiting aerials of Rumex occidentalis (western field dock);

flowering aerials of Rumex occidentalis (western field dock);

fruiting aerials of Rumex pseudonatronatus (field dock);

fruits of Rumex pseudonatronatus (field dock); and

fruits of Rumex stenophyllus (narrow-leaved dock).

The present invention also provides a method for detecting tyrosinaseinhibiting activity in an extract derived from a dicotyledonous plantspecies indigenous to Canada. This method comprises:

a) preparing a first solution comprising an amount of tyrosinase and asuitable substrate;

b) preparing a second solution comprising the same amount of tyrosinaseand the suitable substrate and further comprising an amount of theextract;

c) measuring tyrosinase activities of the first and second solutions bysuitable methods;

d) comparing the tyrosinase activities of the first and secondsolutions; and

e) detecting tyrosinase inhibiting activity, present when the tyrosinaseactivity of the second solution is less than the tyrosinase activity ofthe first solution.

It is preferable that the tyrosinase inhibiting activity is comparableto, or greater than, that of hydroquinone.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is summary of the main steps in the biogenesis of melanin fromtyrosine.

FIG. 2 is a plot of “percent inhibition of enzyme action” vs. log“percent extract in assay reaction mixture” indicating the effectivenessof extracts of Rumex pseudonatronatus, Rumex occidentalis and Oenotherabiennis as tyrosinase inhibitors. Tyrosinase—5 mg.Standard-hydroquinone.

FIG. 3 is a plot of “percent inhibition of enzyme action” vs. log“percent extract in assay reaction mixture” indicating the effectivenessof extracts of Hedysarum americanum and Rosa acicularis as tyrosinaseinhibitors. Tyrosinase—5 mg. Standard—hydroquinone.

FIG. 4 shows the elution profile of whole extract of Rumexpseudonatronatus from a polyvinylpyrrolidone chromatographic column interms of percent inhibition of tyrosinase in the assay. Elution was withwater (ff 1-4) and water-ethanol gradient (ff 5-10).

FIG. 5 shows the effect of alcohol in the extraction solvent ontyrosinase inhibiting activity from Epilobium angustifolium. Epilobiumangustifolium (=WH) was extracted using water (WH-00), 25% ethanol(WH-25), 50% ethanol (WH-50), 75% ethanol (WH-75) and 95% ethanol(WH-95). Each extract was assayed for tyrosinase inhibitory power atthree concentrations. The carrier was butanediol and water.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The definitions of various terms used in this specification appearbelow.

“Plant extracts” are substances obtained from plants by physicalseparation processes such as solvent extraction, steam distillation, orpressing. Broadly, the term “extract” may sometimes be extended toinclude the solvent as well as the plant substance dissolved in it.

The term “screening test” refers to any simple and standardized testwhose purpose is to separate or screen out, from a large number ofmaterials, those unable to perform the function upon which the test isbased, from those able to perform that function.

A typical pilot scale plant extraction method for Rumex species isprovided below.

Ripe, dry (post-season) Rumex species, mostly R. Occidentalis, werefield collected and dry-milled into small fragments. These (250 kg) wereextracted at 70° C. for one hour with 2000 L of approximately 70%ethanol in water. An orange extract was separated from the mash bydecantation and the latter was washed with a further 1000 L of 70%alcohol. The extract liquids were combined, filtered and concentrated to50 L, by which point the ethanol had virtually all been removed andextract solids (content 18-20%) were then beginning to precipitate out.Alternatively, 50 L of glycerol or 1,3-butanediol was added to thepartly concentrated solution to provide a final concentration end-pointvolume of 100 L. This approach avoids precipitation of extract solids.

Carrier glycerol (or 1,3-butanediol) and water were added to theconcentrate to make a red-coloured solution having 5% solids content.Then a further amount of 1:1 glycerol (or 1,3-butanediol)-water carrierliquid was added, amounting to 25% of the weight of the 5% solution anditself containing 5% of L-ascorbic acid (Vitamin C) as an anti-colorantand anti-oxidant. Finally, an anti-microbial preservative, such asphenoxyethanol, was added to a concentration of 0.3 to 0.4%.

The above method provides the basis for the method used to produce theother extracts of the invention. A person skilled in the art willunderstand that variation in certain parameters and substances used inthe method will still produce an extract of the invention.

The tyrosinase assay was based on methods previously published (Mason,H. S., (1948) J. Biol. Chem. 172, 83-86; Dawson, C. R. and Magee, R. J.(1955) Methods in Enzymology II 817-827 (Editors-in-chief S. P. Colowickand N. O. Caplan); Lerner, A. B. (1955) ibid 827-831; Bergmeyer, U. H.(1983) Methods of Enzymatic Analysis (Published by Verlag Chemie,Weinheim)). The protocol was as follows, scaled for the approximatelytwenty sample determinations:

(a) A buffer solution of pH 6.5 was prepared by dissolving 1.4 9disodium monohydrogen phosphate (Na₂HPO₄) and 1.4 g monopotassiumdihydrogen phosphate (KH₂PO₄) in pure water to make 200 mL.

(b) An enzyme solution of either 1.0 mg or 3.0 mg tyrosinase (SigmaT-7755) was prepared in 30 mL buffer and stored at 2° C. until use.

(c) A substrate solution was prepared by dissolving 0.10 g L-DOPA(L-3,4-dihydroxyphenyl-alanine, Sigma D-9661) in 100 ML buffer.

(d) The unfettered enzyme reaction rate was measured by mixing together0.5 mL buffer solution and 0.5 mL substrate solution in twin acrylatemini-cuvettes (path 2.0 mm), and after observing the stability of themixture, mixing in 0.25 mL enzyme solution to one cuvette. The formationof red DOPAquinone was monitored spectrophotometrically at 475 nm, attimes 0, 1, 2 and 3 minutes.

(e) The effect of added substances on the enzyme reaction rate wasmeasured by mixing together 0.5 mL buffer solution, 0.5 mL substratesolution and 0.25 mL test substance (at 1% strength in 50:50butyleneglycol:water) in twin acrylate mini-cuvette. The reaction wastracked spectrophotometrically at 475 nm, reading at 0, 1, 2 and 3minutes.

(f) The effect of test substances on reaction rate was expressed asinhibition (I) where I=100−[100 (trt absorbance change, 3min)/100(control absorbance change, 3 min)].

Concentrations of substrate, enzyme or test substance can be varied asappropriate.

Plant extracts screened by the method of the invention were selectedwhich exhibited tyrosinase inhibiting potency equal to, or better than,hydroquinone. Those extracts are listed in Table 1. The concentrationdependence of the potency of various extracts is summarized in FIGS. 2and 3 in comparison to the concentration dependence of the potency ofhydroquinone.

Table 2 shows the effect of varying the extraction solvent on thetyrosinase inhibiting activity of extracts from three different plantspecies. The effect is also shown by the results in FIG. 5.

TABLE 1 Plant extracts and phytochemicals with tyrosinastatic powerequal to or greater than that of hydroquinone Enzymes reaction ratereduction Plant botanical name @ 5 μg enzyme @ 15 μg enzyme Standard:pure HYDROQUINONE @ 1% Common name Parts used 65% 55% PLANT EXTRACTS OFAmalanchier alnifolia Saskatoonberry flwrg, leaves & twigs 83%, 85% ndArtemisia campestris plains wormwood flowering aerials nd 65% Asterericoides white prairie aster flowering aerials nd 78% Aster hesperiuswillow aster flowering aerials 66% nd Cornus stolonifera red-osierdogwood leaves, twigs, flowers 79% 60% Cotoneaster acutifoliacotoneaster leaves & twigs 65% nd Epilobium angustifolium A firewoodflowering aerials 70% 61% Epilobium angustifolium B firewood floweringaerials 82% nd Euphorbia esula leafy spurge seeding aerials nd 58%Fragaria americana wild strawberry fruiting aerials nd 61% Fragariaglauca wild strawberry fruiting aerials 77%, 68% 72% Geranium bicknelliBicknell's geranium flowering aerials 64% 61% Geum aleppicum yellowavens flowering aerials 78% 67% Geum triflorum 3-flowered avensflowering aerials 78% 71% Glycyrrhiza lepidota A wild licorice floweringaerials 76% nd Hedysarum americanum B American hedysarum floweringaerials 93%, 87%, 90% 88% Heuchera richardsonii alumroot roots 90% 72%Oenothera biennis yellow evening-primrose flowering aerials 82% 67%Polygonum persicaria lady's-thumb flowering aerials 90% 73% Potentillafruticosa shrubby cinquefoil flowering aerials 83%, 78% Potentillanorvegica rough cinquefoil flowering aerials 78% 74% Rosa acicularisprairie rose flowering aerials 83% 83% Rosa arkansana low rose fruitingaerials 81% 61% Rumex maritimus golden dock fruiting aerials 90% 81%Rumex occidentalis A western field dock fruiting aerials 87% 71% Rumexoccidentalis B western field dock flowering aerials nd 82% Rumexpseudonatronatus A field dock fruiting aerials 92% 77% Rumexpseudonatronatus B field dock fruits 88% 70% Rumex stenophyllusnarrow-leaved dock fruits 88% 69%

TABLE 2 Extractability of tyrosinastatic activity from plants The gridnumbers are the percent inhibitions of the enzyme function obtainedusing each extracted solution in two standard tyrosinase assays (5 μgenzyme). Data are corrected for ethanol effects. EXTRACTION SOLVENTSPECIES Ethanol 1:1 Water-ethanol Water Ethyl acetate Epilobiumangustifolium  45%, 39% 65%, 62% 80%, 75% <10% (aerials) Oenotherabiennis <10% 58%, 67% 66%, 63% <101% (aerials) Rumex occidentalis  54%,48% 79%, 79% 81%, 84% <10% (ripe aerials)

There is a very large market for consumer goods containing naturalproducts, such as plant extracts. Compositions for treatment of skin maybe prepared comprising a tyrosinase inhibiting plant extract asdisclosed herein, together with an acceptable diluent or carrier.Acceptable diluent or carriers for cosmetic applications can includesuch substances as water, aqueous alcohols, glycerol, propanediol andbutanediol, as well as certain silicones and waxes. Acceptable diluentsor carriers for pharmaceutical applications are well known in the art.

The tyrosinase inhibiting plant extract can also be used to treat fruit,vegetables or beverages to prevent or reduce browning, since tyrosinaseactivity is a contributor to the browning process. Compositions may beprepared to treat edible products such as fruit, vegetables or beveragesto inhibit browning, which composition comprises a tyrosinase inhibitingplant extract as disclosed herein, together with a diluent or carrierthat is suitable for consumption. The diluent or carrier suitable forconsumption can include such substances as water, aqueous alcohols,propanediol and butanediol, as well as any other suitable substanceacceptable by law.

EXAMPLE 1

A composition known as TYROSTAT-10 (T-10) has the following ingredients:

Purified water 45-50% 1,3-butanediol 45-50% Plant extract solids(Canadian Rumex species) 4.0-4.3% [Rumex occidentals, R.pseudonatronatus, R. stenophyllus and R. martimus] L-Ascorbic acid0.9-1.1% Phenoxyethanol (anti-fungal) 0.2-0.3%

The composition contains no added minerals or other organic materials.It is a readily pourable transparent solution, orange-red coloured at pH4.0-7.5. Upon dilution, the colour moves toward pastel yellow. Thiscolour darkens perceptibly but reversibly at pH values much above 8, andlightens perceptibly on long product storage when sealed from air.

The specific gravity is 1.05 at 21° C.

This material contains natural plant-sourced inhibitors of tyrosinaseenzymes. The potency has been measured using in vitro assays of theconversion of DOPA (3,4-dihydroxyphenylalanine) to the correspondingquinone by the enzyme, in presence and in absence of the TYROSTATproduct and the results are summarized in Table 3. This assay duplicatesrate-controlling steps in the human metabolic pathway to skinpigmentation. Pure hydroquinone in 1% solution was employed as acomparison standard.

TABLE 3 INHIBITION TESTED MATERIAL SOLIDS PRESENT OF ENZYME UndilutedTYROSTAT-10 5% 100% TYROSTAT-10 diluted 10X 0.5 100% TYROSTAT-10 diluted100X 0.05 80-85% Hydroquinone 1.0 58-62%

Rumex extracts appear to inhibit tyrosinase by binding or deforming theenzyme molecule around the active site. Ascorbic acid contributes to theoverall inhibition by maintaining the enzyme's copper atoms in theirreduced Cu⁺ state. Other constituents of TYROSTAT-10 have no significanteffect on tyrosinase in standard assays, although the carrier componentbutanediol is slightly inhibitory. The data in Table 4 indicate therelative capabilities of the active ingredients for tyrosinaseinhibition, at various concentrations of the ingredients.

TABLE 4 Inhibition of tyrosinase enzyme step 2 Ingredient 1% conc 0.1%conc 0.01% conc 0.001% conc Rumex extract 81% 69% 53% 38% Ascorbic acid100% 100% 82% 23% [cf.hydroquinone] 60% 31% <10% <10%

EXAMPLE 2

A composition known as TYROSTAT-11 (T-11) has the following ingredients:

Purified Water 45-50% Glycerol 45-50% Plant extract solids (CanadianRumex 4.0-4.3% species) [Rumex occidentalis, R. pseudonatronatus, R.stenophyllus and R. martimus] L-Ascorbic acid 0.9-1.1% Phenoxyethanol(anti-fungal) 0.2-0.3%

The composition contains no added minerals or other inorganic materials,and no synthetics other than phenoxyethanol preservative. It is areadily pourable transparent solution, orange-red coloured at pH4.0-7.5. Upon dilution, the colour moves toward pastel yellow. Thiscolour darkens perceptibly but reversibly at pH values much above 8, andlightens perceptibly on long product storage when sealed from air.

The specific gravity is 1.15 at 21° C.

This material contains natural plant-sourced inhibitors of tyrosinaseenzymes. The potency has been measured using in vitro assays of theconversion of DOPA (3,4-dihydroxyphenylalanine) to the correspondingquinone by the enzyme, in the presence and in absence of the TYROSTATproduct and the results are summarized in Table 5. This assay duplicatesrate-controlling steps in the human metabolic pathway to skinpigmentation. Pure hydroquinone in 1% solution was employed as acomparison standard.

TABLE 5 INHIBITION TESTED MATERIAL SOLIDS PRESENT OF ENZYME UndilutedTYROSTAT-11 5% 100% TYROSTAT-11 diluted 10X 0.5 100% TYROSTAT-11 diluted100X 0.05 80-83% Hydroquinone 1.0 38-62%

Rumex extracts appear to inhibit tyrosinase by binding or deforming theenzyme molecule around the active site. Ascorbic acid contributes to theoverall inhibition by maintaining the enzyme's copper atoms in theirreduced Cu⁺ state. Other constituents of TYROSTAT-11 have no significanteffect on tyrosinase in standard assays. The data in Table 6 indicatethe relative capabilities of the active ingredients for tyrosinaseinhibition, at various concentrations of those ingredients.

TABLE 6 Inhibition of tyrosinase enzyme step 2 Ingredient 1% conc 0.1%conc 0.01% conc 0.001% conc Rumex extract 81% 69% 53% 38% Ascorbic acid100% 100% 82% 23% [cf.hydroquinone] 60% 31% <10% <10%

Numerous modifications and variations of the present invention arepossible in light of the above teachings. It is therefore to beunderstood that within the scope of the appended claims, the inventionmay be practised otherwise than as specifically described herein.

What is claimed is:
 1. A method of lightening skin, comprising administering to a human subject an effective amount of a Rumex plant extract obtained from a plant or plant part selected from the group consisting of Rumex maritimus (golden dock); Rumex occidentalis (western field dock); Rumex pseudonatronatus (field dock); and Rumex stenophyllus (narrow leaved dock), wherein the plant extract is a substance separated from the plant or plant part by a physical separation process, the physical separation process comprising: (a) solvent extraction; (b) steam distillation; or (c) pressing.
 2. The method of claim 1, wherein the physical separation process comprises solvent extraction.
 3. The method of claim 2, wherein the solvent comprises an alcohol.
 4. The method of claim 2, wherein the solvent comprises an alcohol and water.
 5. The method of claim 1, wherein the physical separation process comprises steam distillation.
 6. The method of claim 1, wherein the physical separation process comprises pressing.
 7. The method of claim 2, wherein the plant extract is obtained from a plant part selected from the group consisting of fruiting aerials of Rumex maritimus (golden dock); fruiting aerials of Rumex occidentalis (western field dock); flowering aerials of Rumex occidentalis (western field dock); an aerial part of Rumex occidentalis (western field dock); fruiting aerials of Rumex pseudonatronatus (field dock); fruits of Rumex pseudonatronatus (field dock); and fruits of Rumex stenophyllus (narrow leaved dock).
 8. The method of claim 7, wherein the plant part is the fruiting aerials of Rumex maritimus (golden dock).
 9. The method of claim 7, wherein the plant part is the fruiting aerials of Rumex occidentalis (western field dock).
 10. The method of claim 7, wherein the plant part is the flowering aerials of Rumex occidentalis (western field dock).
 11. The method of claim 7, wherein the plant part is the fruiting aerials of Rumex pseudonatronatus (field dock).
 12. The method of claim 7, wherein the plant part is the fruits of Rumex pseudonatronatus (field dock).
 13. The method of claim 7, wherein the plant part is the fruits of Rumex stenophyllus (narrow leaved dock).
 14. The method of claim 1, wherein the plant extract is combined with a cosmetically or pharmaceutically acceptable, or edible, diluent or carrier.
 15. The method of claim 1, wherein the plant extract is applied to the skin of the subject.
 16. The method of claim 1, wherein the plant extract is combined with ascorbic acid.
 17. The method of claim 1, wherein the plant extract has a tyrosine inhibiting potency that is at least equal to that of hydroquinone.
 18. The method of claim 2, wherein the plant extract has a tyrosine inhibiting potency that is at least equal to that of hydroquinone.
 19. A method of lightening skin in a subject in need thereof due to accelerated tyrosinase activity, comprising administering an effective amount of Rumex plant extract obtained from a plant or plant part selected from the group consisting of Rumex maritimus (golden dock); Rumex occidentalis (western field dock); Rumex pseudonatronatus (field dock); and Rumex stenophyllus (narrow leaved dock), wherein the plant extract is obtained from the plant or plant part by a physical separation process, the physical separation process comprising: (a) solvent extraction; (b) steam distillation; or (c) pressing.
 20. The method of claim 19, wherein the physical separation process comprises solvent extraction.
 21. The method of claim 20, wherein the solvent comprises an alcohol.
 22. The method of claim 20, wherein the solvent comprises an alcohol and water.
 23. The method of claim 19, wherein the physical separation process comprises steam distillation.
 24. The method of claim 19, wherein the physical separation process comprises pressing.
 25. The method of claim 18, wherein the subject is human.
 26. The method of claim 19, wherein the plant is Rumex occidentalis.
 27. The method of claim 19, wherein the plant extract is combined with a cosmetically or pharmaceutically acceptable₄o edible, diluent or carrier.
 28. The method of claim 19, wherein the plant extract is applied to the skin of the subject.
 29. A method of lightening skin by inhibiting tyrosinase activity in a subject in need thereof, comprising administering an effective amount of Rumex plant extract obtained from a plant or plant part selected from the group consisting of Rumex maritimus (golden dock); Rumex occidentalis (western field dock); Rumex pseudonatronatus (field dock); and Rumex stenophyllus (narrow leaved dock), wherein the plant extract is obtained from the plant or plant part by a physical separation process, the physical separation process comprising: (a) solvent extraction; (b) steam distillation; or (c) pressing.
 30. The method of claim 29, wherein the physical separation process comprises solvent extraction.
 31. The method of claim 30, wherein the solvent comprises an alcohol.
 32. The method of claim 30, wherein the solvent comprises an alcohol and water.
 33. The method of claim 29, wherein the physical separation process comprises steam distillation.
 34. The method of claim 29, wherein the physical separation process comprises pressing.
 35. The method of claim 29, wherein the subject is human.
 36. The method of claim 29, wherein the plant is Rumex occidentalis.
 37. The method of claim 29, wherein the plant extract is combined with a cosmetically or pharmaceutically acceptable, edible, diluent or carrier.
 38. The method of claim 29, wherein the plant extract is applied to the skin of the subject. 